We have been studying the role that protein degradation plays in regulating cell growth control, through the study of mutants defective in ATP-dependent protein degradation. E. coli lon mutants are defective in cell division regulation after DNA damage, and we have previously demonstrated that this defect is due to stabilization of a highly unstable cells division inhibitor, the product of the SulA gene. lon mutants also overproduce capsular polysaccharide; we have identified three regulatory genes which participate in the regulation of cps (capsule synthesis) genes. The protein products of two positive regulatory loci, rcsA and rcsB, have been identified. RcsA is unstable, and its turnover may be mediated by the Lon protease; RcsB is stable. The third regulatory locus, rcsC, serves as a negative regulator of the system, but may have additional roles as well. We have used the in vitro degradation of the Lon substrates lambda N protein, insulin B chain, and glucagon, to define the sites of Lon cleavage. While Lon has preferred sites of cleavage on these molecules, the preferred sites do not represent any simple amino acid sequence. Studies on cells devoid of Lon activity demonstrate the existence of other ATP-dependent proteolysis systems in E. coli. A genetic selection for mutants with increased activity for other proteases has been developed, by selecting for mutants resistant to the unstable cell division inhibitor, SulA. Mutant candidates which are resistant to high levels of SulA apparently increase proteolysis. Mapping studies, now in progress, should allow the identification of the proteases involved. Using a biochemical screen for the ATP-dependent degradation of casein, we have identified a new, multi-component ATP-dependent protease in cells devoid of Lon activity.